tbuckley/cabot-search huggingface dataset:
Medically integrated dispensing (MID) clinical and cost outcomes compared to specialty pharmacies (SP).
Authors: Joseph W. Leach, David Eckwright, Steven W. Champaloux, Paul Forsberg, Arno Weiss, Christopher Jorgensen, Patrick P. Gleason
Journal: Journal of Clinical Oncology (2022)

e18645 Background: Oral oncolytics MID offers potential care and cost advantages compared to a centralized SP model. A pharmacy benefit manger and 3 health plans created a pilot program to enable and encourage oncology practice MID with the goal of improving care, enhancing the provider and patient experience, and reducing drug waste. This study assesses clinical outcomes and drug waste differences between MID and central SP dispensing using real-world pharmacy claims data. Methods: The MID pilot program was implemented early 2021 within 3 oncology practices across 3 plans commercially insured lives. Members were required to have continuous enrollment for the adherence and discontinuation (d/c) measures. Adherence was measured using the CMS industry standard proportion of days covered with a &gt; / = 80% cut point. D/c was measured in new initiators defined as no claim evidence of the drug in the previous 90 days with discontinuation defined as having a &gt; / = 45-day therapy gap within the first 180 days. Dose changes were defined as a new unit strength being dispensed for a previously filled drug. Each measure used a unique drug list: 3 CDK4/6i for adherence; 10 highly utilized oral brand and generic oncolytics for d/c; and 26 oral oncology brand drugs having multiple strengths and labeled dose change directions for dose change waste. The adherence and waste measures assessment end date was Dec 31, 2021 and for d/c was Jan 28, 2022. Statistical testing: adherence- Fischer’s exact test; d/c- chi-square; and waste– t-test. Results: For adherence, individuals were followed for an average of 243 days, range 21-333 days, without a statistical difference between MID and SP follow-up. CDK4/6i adherence was 82% (9 of 11) for MID and 73% (421 of 574) for SP, p = 0.74. D/C was 29% (15 of 52) for MID and 48% (360 of 753) for SP, p = 0.01. Waste occurred in 29% (6 of 21) of MID dose changes and 50% (315 of 627) of SP dose changes, p = 0.05; resulting in an average cost of $937 and $2,733 per dose change at the MID and SP, respectively, for an SP average dose change additional cost of $1,796. Conclusions: MID demonstrated numerically higher adherence, significantly lower d/c rate with MID having a number need to treat of 5 to prevent one less d/c event, and significantly lower waste expense with an estimated savings of $1.1 million, if all 627 individuals with a dose change at SP had used a MID. These real-world findings have resulted in a national PBM network to encourage MID use.
Obesity diabetes and dyslipidemia as determinants of immune checkpoint inhibitors response in non-small cell lung cancer.
Authors: Muhammad Awidi, Soravis Osataphan, Yu Jen Jan, Edward Frankenberger, Melissa Mariano, Katherine Ann Stafford, Aleksandra Kolnick, Hind Ghazalah, Mary-Elizabeth Patti, Krishna Soujanya Gunturu, Prudence B. Lam
Journal: Journal of Clinical Oncology (2022)

e21104 Background: Immune checkpoint inhibitors (ICI) are standard of care in the treatment of non-small cell lung cancer (NSCLC). Predictive markers of response to ICI are being studied extensively. Obesity has been correlated with a better response to ICI in NSCLC and other types of cancer. This may in-part be related to high circulating leptin or impaired T-cell fatty acid oxidation within the tumor microenvironment. We aim to further explore the effects of obesity, dyslipidemia and other components of the metabolic syndrome such as diabetes on treatment outcomes on NSCLC patients receiving ICI. Methods: We conducted a retrospective cohort study in patients with NSCLC treated with pembrolizumab, nivolumab, durvalumab, cemiplimab or atezolizumab as monotherapy or combined with chemotherapy at Mount Auburn and Lahey Hospital between January 2016 to June 2021. Obesity was defined as body mass index (BMI) &gt; 30 kg/m2, dyslipidemia and type 2 diabetes were defined by ICD-10 diagnosis codes. Overall survival was evaluated. Kaplan-Meier survival analysis and cox proportional hazards regression were used to assess correlation between overall survival and obesity, dyslipidemia, type 2 diabetes, metformin use and statin use. These were adjusted for age, biological sex, cancer stage, ECOG and smoking status. Patients with BMI &lt; 18.5 were excluded. Results: We identified 408 patients with NSCLC who were treated with ICIs. Of these, 66.7% had adenocarcinoma, 29.1% had squamous and 4.2% had either adenosquamous, large cell or poorly differentiated carcinoma. Among these patients 23.3% were classified as obese, 55.6% had dyslipidemia and 23% had type 2 diabetes. Of these, 66% of patients received ICIs as monotherapy. Median survival was 840 days in obese patients compared to 483 days in non-obese patients (HR 0.66, CI 0.42-0.92, p = 0.014). Conversely, within this cohort, median survival in patients with dyslipidemia was 483 days when compared to 762 days in controls (HR 1.37, CI 1.07-1.81, p = 0.013). Overall survival was not significantly different between type 2 diabetes, metformin use or statin use. Conclusions: Our study shows a trend towards a better survival in obesity and poor survival associated with dyslipidemia. Obesity and dyslipidemia may be important markers of ICI response in patients with NSCLC regardless of treatment strategies. Further studies are needed to explore the molecular mediators within the metabolic syndrome that may provide a synergistic effect with immune checkpoint inhibitors.
Prospective evaluation of an affordable and portable artificial intelligence-based modality for breast cancer screening in women across breast densities.
Authors: Richa Bansal, Bharat Aggarwal
Journal: Journal of Clinical Oncology (2022)

e13585 Background: Mammography is known to be less effective in women with dense breast. Thermalytix is a radiation-free technique for breast screening which uses artificial intelligence over thermal images and has shown promising results in early clinical results. Methods: A prospective, cross-sectional study was conducted from December 2018 to January 2020 to compare the performance of Thermalytix with Mammography in women with dense and non-dense breast tissue. Women aged between 30 and 80 years who presented for a routine health check-up to the hospital and provided informed written consent for the study were included in the evaluation. All women took both Thermalytix and 2D-mammography tests. The output of the Thermalytix tool was blinded to the radiologist interpreting mammograms and the Thermalytix technician did not have access to any other imaging reports of the patient . For participants who were reported as positive on either or both of the tests, confirmatory diagnostic investigations were recommended; the outcome of which was used as the ground truth for comparison. Sensitivity and specificity of the two tests were calulated across age-groups, menopausal status, and breast densities.. Results: Among the 687 women invited for the study, 459 women fulfilled the inclusion criteria for the study analysis. Overall, 21 women were diagnosed with breast malignancies in the study. Thermalytix demonstrated an overall sensitivity of 95·24% (95% CI, 76·18-99·88) and a specificity of 88·58% (95% CI, 85·23-91·41). In 168 women (36·6%) who had ACR categories ‘c’ or ‘d’ dense breasts, Thermalytix showed a sensitivity of 100% (95% CI, 69·15-100) and specificity of 81·65% (95% CI, 74·72-87·35). Among these 168 women, 37 women had an incomplete assessment (BI-RADS 0) of their mammograms with a single reader (trained radiologist), while all 3 malignancies in these women were identified by Thermalytix tool. Conclusions: Thermalytix has the potential to be a radiation-free, privacy-conscious modality for breast cancer screening. Particularly in women with dense breast tissue, it can be a supplemental modality to mammography. As an automated, portable and affordable solution, Thermalytix test could be used alone for large-scale breast cancer screening programmes in resource-constrained settings. Clinical trial information: NCT04688086.
HGG-24. NTRK-rearranged infantile gliomas of suprasellar/ optic pathway origin
Authors: Margot A Lazow, Mariam Mathew, Ralph Salloum, Diana P Rodriguez, Jeffrey Leonard, Susan Chi, Diana Thomas, Catherine Cottrell, Maryam Fouladi, Daniel R Boué
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Oncogenic fusions involving neurotrophic tyrosine receptor kinase (NTRK) have been identified across cancer types and represent potential therapeutic targets given availability of TRK inhibitors. Gliomas harboring NTRK fusions have been described most commonly in infants with high-grade histology and hemispheric tumor location, though there is emerging evidence suggesting clinical, histopathologic, and molecular heterogeneity. Herein, we present two cases of NTRK-rearranged suprasellar/ optic pathway gliomas. CASE DESCRIPTIONS: The first patient was diagnosed at 6 months old with an extensive suprasellar/ optic pathway tumor, treated with carboplatin/ vincristine, which initially responded but subsequently progressed. A biopsy was then performed, with pathology consistent with infiltrating piloid astrocytoma with anaplastic features (elevated mitoses and Ki-67 index); a BCAN-NTRK1 fusion was identified by RT-PCR and confirmed by Sanger sequencing. After further disease progression on vinblastine monotherapy, this patient began treatment with entrectinib (NCT02650401), with favorable clinical and radiographic responses thus far. The second patient was diagnosed with a large suprasellar/ optic pathway tumor at 3 years old, and underwent upfront partial resection, revealing similar infiltrating piloid/pilocytic astrocytoma with anaplastic features (elevated mitoses and Ki-67 index). A diagnosis of “midline” infantile high-grade glioma (HGG) was also considered, as with the former case. Sequencing demonstrated a SOX10-NTRK3 rearrangement, resulting in an integrated diagnosis of NTRK-fused infantile HGG, for which the patient recently started treatment with larotrectinib (NCT04655404). Both patients’ fusions retain the entire kinase domain of respective NTRK partners, supporting oncogenicity, and neither tumor harbored additional somatic pathogenic variants (both lacked BRAF alterations). Methylation profiling did not confidently classify either tumor. CONCLUSIONS: NTRK-rearranged gliomas may present with primary suprasellar/ optic pathway involvement in infants. Given the potential to offer targeted therapy, testing for the presence of NTRK fusions should be strongly considered for infantile gliomas in any location, including midline, and across the histologic spectrum.
Cancer Screening and Surveillance Testing for Older Adult Cancer Survivors
Authors: Nancy L. Keating
Journal: Journal of the National Comprehensive Cancer Network (2022)

In older adult cancer survivors, cancer screening and surveillance testing carry benefits and harms that depend on a variety of factors. Benefits of screening include early diagnosis and a lower risk of death from cancer. Harms include false-positive results, unnecessary biopsies, incidental findings, and overdiagnosis. The primary factor in deciding whether older adult cancer survivors should undergo screening or surveillance testing is life expectancy, but other factors also come into play, such as a patient’s health status, goals, and values. An individualized approach as well as shared decision-making are crucial when working with patients to make these important decisions.
A phase I/II multisite study of rucaparib and pembrolizumab maintenance therapy in stage IV non-squamous non–small cell lung cancer after initial therapy with carboplatin, pemetrexed, and pembrolizumab.
Authors: Angel Qin, Daniel Morgensztern, Saiama Naheed Waqar, Dwight Hall Owen, Shirish M. Gadgeel, Gregory Peter Kalemkerian, Lili Zhao, Nithya Ramnath
Journal: Journal of Clinical Oncology (2022)

TPS9138 Background: Carboplatin, pemetrexed, and pembrolizumab (CPP) followed by pemetrexed and pembrolizumab maintenance is a standard of care (SOC) for non-squamous metastatic non-small cell lung cancer (NSCLC), based on results of the KEYNOTE-189 study. The progression free survival (PFS) on this study was 8.8 months. There is increasing data to support that certain sporadic tumors harbor somatic mutations in genes of the homologous recombinant repair (HRR) pathway resulting in a “BRCAness” phenotype rendering sensitivity to PARP inhibitors (PARPi). TCGA data suggest up to 38% of NSCLC have mutations in HRR pathway genes. Furthermore, treatment with PARPi is shown to upregulate PD-L1 expression, which is associated with pembrolizumab response in NSCLC. We therefore hypothesized that maintenance therapy with a PARPi and pembrolizumab will improve PFS compared to SOC pemetrexed and pembrolizumab. Methods: This is a single arm, multi-site, investigator-initiated phase I/II study that is enrolling treatment-naïve patients with stage IV nonsquamous metastatic NSCLC without any targetable driver mutations eligible for CPP. Patients without progression after 4 cycles of CPP then proceed to maintenance with rucaparib 600mg PO BID and pembrolizumab 200mg IV every 21 days. The primary objective is efficacy assessed by PFS and second objectives include overall survival, safety, tolerability, and objective response rate (ORR). Correlatives in this study include PD-L1 expression, tumor mutational burden (TMB), and measurements of HRR deficiency as assessed by homologous repair deficiency (HRD) and loss of heterozygosity (LOH) using established methods. Key exclusion criteria include untreated brain metastases and prior exposure to a PARPi or PD-1/PD-L1 inhibitor. The phase I cohort which consisted of 6 patients treated with the approved full doses of rucaparib and pembrolizumab was completed without dose limiting toxicity (DLT). Using a Bayesian decision-theoretic two-stage design, the first stage will enroll 38 patients. If predefined PFS parameters are met, an additional 17 patients, for a total of 55 patients, will be enrolled. To date, 21 patients have been enrolled. Clinical trial information: NCT03559049.
Dysregulation of immune checkpoint proteins in patients with newly diagnosed early breast cancer.
Authors: Bernardo Leon Rapoport, Helen C. Steel, Carol Benn, Simon Nayler, Teresa Smit, Liezl Heyman, Annette J. Theron, Nomsa Hlatswayo, Luyanda LI Kwofie, Pieter Meyer, Ronald Anderson
Journal: Journal of Clinical Oncology (2022)

3044 Background: Checkpoint proteins regulate the immune system. Breast cancer (BC) cells can up-regulate or down-regulate these proteins to evade anti-tumor immune responses. Soluble forms of immune checkpoint molecules (ICMs) can be measured in human plasma. The study aimed to measure the systemic levels of a series of co-stimulatory and co-inhibitory ICMs at diagnosis, post-neo-adjuvant chemotherapy (NAC) and post-surgery in newly- diagnosed BC patients (pts) relative to those of a healthy control group. Methods: Soluble ICMs were measured using multiplex bead array technology in plasma from 72 BC pts and 45 healthy controls. Data was prospectively obtained and levels compared between pre-treatment, post-NAC, and post-surgery using non-parametric tests (Mann-Whitney &amp; Kruskal-Wallis). Results: Pre-treatment levels of the soluble stimulatory molecules viz. GITR (p&lt;0.0001), GITRL (p&lt; 0.020), CD27 (p&lt; 0.024), CD40 (p&lt; 0.021), ICOS (p&lt; 0.009), as well as the inhibitory molecules PD-L1 (p&lt; 0.0001), CTLA-4 (p&lt; 0.005), TIM-3 (p&lt; 0.0004), HVEM (p&lt; 0.0004) were significantly lower in early BC pts compared to controls. Post-treatment, there were significant increases in most ICM levels (Table), with the exception of CTLA-4, which decreased significantly following treatment. On the other hand, pre-treatment plasma concentrations of CCL5 (RANTES) (84.22 vs. 48.72 pg/mL, p&lt;0.0001), M-CSF (84.41 vs 13.34 pg/mL, p&lt;0.0001), FGF-21 (24.36 vs. 8.64 pg/mL, p&lt;0.001) and GDF-15 (806.82 vs. 430.03 pg/mL, p&lt;0.0001) were significantly increased in the breast cancer pts compared to healthy controls. A pathological complete response (pCR) was documented in 65% of pts (mostly TNBC). There were no correlations between pre-treatment ICM levels, CCL5, M-CSF, FGF-21 and GDF-15 and pCR. Conclusions: We identified low levels of stimulatory and inhibitory ICMs in newly-diagnosed, non-metastatic BC pts compared to healthy controls. Following treatment, with the exception of CTLA-4, most of these pre-treatment abnormalities of systemic ICM levels corrected. NAC is associated with upregulation of sPD-L1 and most other ICMs. These results indicate that early BC is associated with down-regulation of soluble stimulatory and inhibitory ICMs. Newly-diagnosed early BC pts appear to have generalized immune-suppression independent of subtype and stage. To our knowledge, this is the first study to describe the effect of treatment on systemic ICMs in early BC pts. [Table: see text]
Post hoc analysis of a long-term safety extension study: Responses to siltuximab in idiopathic multicentric Castleman disease patients receiving on-label dosing.
Authors: Jean-Francois Rossi, Pier Luigi Zinzani, Corey Casper, Peter M. Voorhees, Luis Fayad, Karan Kanhai, Razelle Kurzrock, Frits Van Rhee
Journal: Journal of Clinical Oncology (2022)

e19586 Background: Siltuximab is the only FDA- and EMA-approved therapy for idiopathic multicentric Castleman disease. Its long-term efficacy and safety were established in a 6-year extension study featuring patients who responded to treatment or had stable disease in a phase 1 or phase 2 trial. However, dosage could be adjusted at physician discretion; of 60 patients, 33 remained on the on-label dosing of 11 mg/kg administered every 3 weeks. To assess the safety and efficacy of on-label dosing, we performed a post hoc analysis in patients who maintained this dosing. Methods: A mixed-effects model was used to analyze longitudinal measurements for tumor response, C-reactive protein (CRP), hemoglobin (Hb), erythrocyte sedimentation rate (ESR), fibrinogen, albumin, and platelet counts at multiple time points. Adverse events (AEs) were also assessed. Greenhouse–Geisser correction was used to ensure that the assumption of sphericity was met for the mixed-effects model. Tukey post hoc correction was applied to determine significant differences between specific time points. Results: Of the 33 patients on 3-week dosing, one transitioned to receiving siltuximab every 6 weeks for 25 cycles but restarted 3-weekly dosing due to suspected progressive disease (PD). Disease control was observed in 31 of the 33 patients (93.9%) at their last on-study assessment (complete response [CR] in 9 [27.3%]). Quantitative analyses were performed on the 32 patients who maintained 3-weekly dosing until their last on-study assessment. Siltuximab led to sustained mean levels of CRP, Hb, ESR, fibrinogen, albumin, and platelet counts for the duration of the study. In the 19 patients with residual IL-6 activity at screening (CRP levels &gt; 4 mg/L) there was an overall reduction in CRP from baseline at multiple time points. This group showed a trend towards improved total Hb levels, which increased by 9.43% (adjusted p = 0.048) at cycle 31, and some demonstrated an improvement in ESR, fibrinogen, and albumin levels. All patients reported AEs, mostly grade 1 or 2, with no deaths. At point of enrolment into the extension study, the three most common AEs were hypertension (36.4%), fatigue (42.4%), and pain (51.5%). Conclusions: Our findings show that long-term on-label dosage of siltuximab sustains an improved inflammatory profile and disease control.[Table: see text]
Considerations for Generic-to-Generic Levothyroxine Switching—Reply
Authors: Juan P. Brito, Zhong Wang, Kasia J. Lipska
Journal: JAMA Internal Medicine (2022)

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OTHR-15. Papillary tumor of the pineal region: case series of this rare pediatric entity
Authors: Margaret Shatara, Evan Cantor, Ashley Meyer, Andrea Ogle, Tammy Green, Mary Beck, Michele McHugh, Nicole Brossier, Andrew Cluster, Joshua Rubin, Ali Mian, Sonika Dahiya, Stephanie Perkins, Mohamed S Abdelbaki, Jennifer Strahle, David Limbrick, Sean D McEvoy
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: The optimal management of pediatric papillary tumors of the pineal region (PTPR) is not yet established. We report three cases, as an addition to the existing literature. PATIENT 1: A 22-month-old female presented with progressive ataxia and incoordination, found to have an enhancing solid and cystic mass centered within the pineal region, with associated obstructive hydrocephalus. Tumor biopsy revealed PTPR, prompting a subsequent subtotal resection. No adjuvant therapy was recommended. Patient has remained without evidence of disease progression for 92 months, since resection. PATIENT 2: An 8-year-old female presented with progressive headaches and new-onset generalized seizures, found to have a heterogeneously enhancing pineal lesion, with associated obstructive hydrocephalus. Following a biopsy demonstrating PTPR, patient underwent subtotal resection of the tumor. A second resection was completed 6 months later followed by focal irradiation. Targeted next-generation sequencing (NGS) demonstrated two non-targetable genomic alterations (CREBBP and MLL2). The patient remains without tumor recurrence, now 37 months, since irradiation. PATIENT 3: A 7-year-old male with Autism spectrum disorder presented with new-onset focal complex seizures. A brain MRI showed a heterogeneously enhancing lesion in the region of the pineal gland, with associated obstructive hydrocephalus. A tumor biopsy revealed PTPR, prompting a subsequent gross total resection (GTR). NGS demonstrated no reportable genomic alterations. Methylome profiling classified the tumor as PTPR, group B. Post-operative imaging with no residual tumor and he has remained without tumor progression, now eight months, since resection. CONCLUSION: PTPR are extremely rare in the pediatric setting, and were initially introduced in the WHO 2007 classification as grade II-III pineal gland tumors with distinct morphologic and immunohistochemical features. GTR is the mainstay of treatment but post-surgical management remains controversial. The clinical course is characterized by frequent local recurrence, hence, adjuvant chemotherapy and/or irradiation may be necessary upon disease progression.